Contents

‡ Bones Muscoloskeletal System „ Osteoporosis „ Rickets, osteomalacia, hyperparathyroidism, renal osteodystrophy Sakchai Chitpakdee, M.D. „ Fracture „ Osteonecrosis (Avascular necrosis) „ Infections „ Bone tumors and tumor-like lesions

Contents Osteoporosis

‡ Joints ‡ Increased porosity of skeleton resulting „ Arthritis and osteoarthritis from reduced bone mass „ Tumor and tumor-like lesions of joints „ Localized: disused osteoporosis ‡ Skeletal muscle „ Generalized: metabolic bone disease ‡ Primary: Senile, postmenopausal, idiopathic „ Muscular dystrophies ‡ Secondary: Vit D deficiency, Steroids „ Inflammatory myopathies ‡ Most common: „ Myasthenia Gravis „ Senile osteoporosis „ postmenopausal osteoporosis

Osteoporosis

‡ Clinical course: „ Veterbral fractures: thoracic and lumbar regions, painful „ Multiple fractures Æ loss of height, lumbar lordosis and kyphoscoliosis ‡ Diagnosis: „ 30-40% bone loss Æ detected by radiographs „ Dual-energy absorption and quantitative CT „ Biopsy Osteoporosis

‡ Prevention and treatment: „ Exercise „ Calcium and vitamin D intake „ Estrogen replacement „ Biphosphonate „ Recombinant PTH

Rickets and Osteomalacia Hyperparathyroidism

‡ Defect in matrix mineralization ‡ PTH Æ ↑osteoclastic activity ‡ Lack of vitamin D or disturbance of its ‡ Osteitis fibrosa cystica (brown tumor) metabolism ‡ Clinical features: ‡ Children Æ “rickets” „ Fracture, bone deformities „ Skeletal deformities „ Joint pain and dysfunction ‡ Adults Æ “osteomalacia” „ Osteopenia Æ fracture

Renal Osteodystrophy

‡ Skeletal changes of chronic renal disease: „ High turnover osteodystrophy ‡ ↑Osteoclastic bone resorption (osteoporosis) „ Low turnover or aplastic disease ‡ ↓Matrix mineralization (osteomalacia) ‡ Pathogenesis: „ Vitamin D def. Æ hypocalcemiaÆ PTH ↑ „ Hyperphosphatemia Æ PTH ↑ „ Metabolic acidosis Æ bone resorption ↑ „ Aluminum deposit Æ bone mineralization ↓ Fractures Fractures

‡ Classification: ‡ Reparative process: st „ Complete vs. incomplete ‡ 1 week Æ organizing hematoma (soft tissue callus, procallus) „ Closed (simple) vs. Opened (compound) ‡ 2nd or 3rd week Æ bony callus (cartilage and bone „ Comminuted (splintered) formation) „ Displaced ‡ Delayed healing: Æ nonunion „ Pathologic fracture (underlying bone dis.) ‡ Displaced, comminuted, compound fractures „ Stress fracture (repetitive loads) ‡ Inadequate immobilization ‡ Infections ‡ Calcium↓, phophorus↓, Vitamin def. diabetics, vascular insufficiency

Osteonecrosis (AVN)

‡ Ischemia Æ infarction ‡ Mechanisms: „ Vascular interruption (fracture) „ Corticosteroids „ Thrombosis and embolism (nitrogen bubbles, dysbarism) „ Vessel injury (vasculitis, radiation) „ ↑ Intraosseous pressure and vascular compression „ Venous hypertension

Osteonecrosis (AVN) Infections—Osteomyelitis

‡ Clinical course: ‡ Pyogenic osteomyelitis „ Subchondral infarcts Æ chronic pain, 2nd „ Bacterial infections: osteoarthritis ‡ S. aureus (80-90%) „ Medullary infarcts Æ clinically silent, painful, ‡ E. coli, Pseudomonas, Klebsiella: IVDU, GU tract collapse ‡ Mixed organisms: fracture, direct spread ‡ H. influenzae: neonatal period

‡ Salmonella: sickle cell anemia „ Spread: hematogenous, extension from contiguous sites, direct implantation Infections—Osteomyelitis

‡ Pyogenic osteomyelitis „ Sites: ‡ Neonate: Metaphysis, epiphysis

‡ Children: Metaphysis ‡ Adult: Epiphysis, subchondral „ Clinical course: ‡ Acute systemic illness, fever, malaise, leukocytosis, throbbing pain ‡ X-ray: lytic bone destruction

‡ Threatment: antibiotics and surgical drainage ‡ 5-25% Æ chronic osteomyelitis

Infections—Osteomyelitis Bone tumors and Tumor-like lesions

‡ Tuberculous osteomyelitis ‡ Hematopoietic (40%) „ 1-3% of patients with pulmonary or ‡ Chondrogenic (22%) extrapulmonary TB have osseous infection ‡ Osteogenic (19%) „ Hematogenous spread from visceral organs or direct extension ‡ Unnown origin (10%): giant cell tumor „ Spine infection (Pott disease): thoracic and ‡ Micellaneous: lumbar vertebrae „ Fibrous and histiocytic „ More destructive and resistance to therapy „ Vascular than pyogenic osteomyelitis „ Lipogenic „ Neurogenic

Bone tumors and Tumor-like lesions Bone-forming tumor

‡ Characteristic: ‡ Osteosarcoma: „ Osteosarcoma: „ Most common primary bone tumor ‡ Adolescence, metaphysis around the knees „ Age: 75% (children, <20 yo) 25% (elderly) „ Chondrosarcoma „ Secondary osteosarcoma: Paget disease, bone ‡ Adulthood, trunk, limb girdle, proximal long bones infarct, irradiation „ Giant cell tumors and chondroblastoma: „ Sites: metaphyseal region of long bone ‡ Epiphysis of long bones „ Clinical: painful enlarging mass „ Ewing sarcoma, osteofibrous dysplasia, „ X-ray: destructive, lytic and blastic mass with adamantinoma permeative margin, “Codman Triangle” ‡ Diaphysis „ Treatment: Chemotherapy, limb salvage Cartilage-forming tumor

‡ Osteochondroma: „ Exostosis „ Solitary and multiple (hereditary) „ Late adolescence and early adulthood „ Metaphysis of long bones „ Clinical: slow-growing mass, can be painful, rare (<1%) Æ chondrosarcoma

Cartilage-forming tumor

‡ Chondrosarcoma: „ Second most common malignant matrix- producing tumor of bones „ Age 40 or older „ Malignant transformation from enchondroma, osteochondroma, chondroblastoma „ Sites: central portions of skeleton, pelvis, shoulder, and ribs „ Clinical: painful enlarging mass, fracture „ X-ray: Destructive radiolucent mass „ Treatment: Surgical excision, chemotherapy

Miscellaneous tumors

‡ Giant cell tumor: „ Benign but locally aggressive tumor „ Patients in twenties to forties „ Sites: epiphysis and metaphysis of any bones (common: distal femur and proximal tibia) „ X-ray: large, purely lytic, eccentric and erode into subchondral bone plate „ Treatment: Conserative surgery „ 40-60% recurrent, 4% metastasis to lung Metastatic disease

‡ Adults: „ Prostate, breast, kidney, and lung ‡ Children: „ Neuroblastoma, Wilms tumor, osteosarcoma, Ewing sarcoma, rhabdomosarcoma ‡ X-ray: „ Multifocal or solitary (kidney, thyroid)

‡ Lytic: Kidney, lung, GI and melanoma ‡ Blastic: Prostate

Joints Osteoarthritis

‡ Osteoarthritis: ‡ Pathogenesis: „ Degenerative joint disease „ Aging and mechanical effects „ Progressive erosion of articular cartilage „ Genetic factors: high bone density „ Idiopathic (primary OA): aging phenomenon ‡ Clinical course: „ Secondary oateoarthritis (5%): diabetics, „ Primary OA: old age (>50 yr) ochronosis, hemochromatosis, obesity „ Secondary OA: younger age, underlying dis. „ Women: knees and hands „ Deep achy pain, worsen with use „ Men: hips „ Morning stiffness, crepitus, limitation of movement „ Nerve root compression (osteophytes)

Rheumatoid arthritis

‡ Chronic systemic inflammatory disorder: skin, blood vessels, heart, lungs, muscles, joints ‡ Pathogenesis: „ Autoimmune disease: arthritogenic antigen Æ CD4+ helper T cells Æ inflammatory cytokines „ Genetic susceptibility: HLA-DR1*0401, *0404 „ Antigens: unknown Rheumatoid arthritis

‡ Clinical course: „ 50%, slow and insidious onset: malaise, fatigue, musculoskeletal pain, joint pain „ 10% acute onset with sever symptoms „ Site: small joints > large joints: MCP, PIP, MTP, IP, wrists, ankles, elbows, knees „ 20%, partial or complete remission period „ Joint destruction, deformity: swan neck, boutonniere of fingers „ X-ray: juxta-articular osteopenia, bone erosion with narrowing of joint space

Rheumatoid arthritis

‡ Laboratory tests and Dx: „ Serum rheumatoid factor (IgM to Fc portion): not specific „ Synovial fluid analysis: inflammatory exudate „ Clinical criteria: 4 criteria ‡ Morning stiffness ‡ Arthritis in three or more joints ‡ Arthritis of typical hand joints ‡ Symmetric arthritis ‡ Rheumatoid nodules ‡ Serum rheumatoid factor ‡ Typical radiographic changes

Rheumatoid arthritis Seronegative spondyloarthropathies

‡ Treatment: ‡ Ankylosing spondylitis „ Anti-inflammatory drugs (aspirin, NSAIDs) ‡ Reactive arthritis (Reiter syndrome and „ Steroids enteritis associated arthritis) „ Anti-TNF antibody, soluble TNF receptor ‡ Psoriatic arthritis ‡ Arthritis associated with inflammatory bowel disease Ankylosing spondyloarthritis Reactive arthritis

‡ Rheumatoid spondylitis and Marie- ‡ Noninfectious arthritis of appendicular Strumpell disease skeleton occurs within one months of ‡ Sites: axial, sacriiliac & apophyseal joints primary infection localized elsewhere „ GU: clamydia ‡ Age: 20-30 yr, M>F „ GI: shigella, salmonella, Yersinia, ‡ 90% HLA-B27 positive Campylobacter ‡ Clinical: low back pain, spinal immobility „ Reiter syndrome: arthritis, nongonococcal (ankylosis), fracture of spine, aortitis, urethritis/cervicitis, conjunctivitis amyloidosis „ 80% HLA-B27 positive „ Extraarticular: balanitis, carditis

Infectious arthritis Gout and Gouty arthritis

‡ Suppurative arthritis: ‡ Transient attacks of arthritis initiated by „ Bacteria: gonococcus, Staphylococcus, crystallization of monosodium urates Strepcoccus, Haemophilus influenza, E. coli, (needle shape, neg. birefringent) within salmonella, Pseudomonas joints „ Children <2 yr: H. Influenzae ‡ Pathogenesis: hyperuricemia Æ gout „ Adults: S. aureus „ Age: 20-30 yr after hyperuricemia „ Young women: Gonococcus „ Genetic: Lesch-Nyhan syndrome „ Heavy alcohol consumption „ Sickle cell anemia: Samonella „ Obesity „ Painful joint, fever, leukocytosis „ Drugs: thiazides „ Knees, hip, shoulder, elbow, wrist „ Lead toxicity

Gout and Gouty arthritis

‡ Clinical course: four stages „ Asymptomatic hyperuricemia: puberty male or menopause women „ Acute gouty arthritis: 50% MTP joint, ankles, heels, knees, wrists, fingers, elbows „ Intercritical gout „ Chonic tophaceous gout: 12 years after first attack „ Extra-articular: atherosclerosis, hypertension, renal colic, gouty nephropathy Pseudogout

‡ Calcium pyrophosphate crystal deposit disease (CPPD) ‡ Age: over age 50 ‡ Type: Idiopathic, hereditary and secondary (joint damage, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism) ‡ Clinical: aymptomatic, acute, sunacute, chronic arthritis of knees, wrists, elbows, shoulder, ankles

Tumor and Tumor-like lesions

‡ Ganglion cysts: „ Size: 1 to 1.5 cm near joint capsule or tendon „ Site: wrists, fingers „ Etiology: Cystic degeneration ‡ Synovial cysts: „ Baker cyst of knees in RA patients „ Synovial protrusion (diverticulum)

Muscular dystrophies

‡ X-linked muscular dystrophy (Duchene and Becker muscular dystrophy) „ Pathogenesis: Dystrophin gene, Xp21 ‡ Deletion or frameshift mutation (DMD), Point mutation (BMD) „ Clinical: ‡ DMD normal at birth, delayed walking, clumsiness ‡ Weakness begins in pelvic girdles, shoulder girdles ‡ Enlargement of calf muscle (pseudohypertrophy) ‡ Increased serum creatine kinase ‡ Death from respiratory failure, pulmonary infection and cardiac decompensation ‡ BMD: later onset and less severe Myasthenia gravis Reference

‡ Immune-mediated loss of acetylcholine ‡ Kumar, Kabbas, fausto: Robbins and resectors (AChRs); autoimmune disease Cotran Pathologic Basis of Disease: 7th ed ‡ W>M, Age < 40 ‡ http://www.pathguy.com/lectures/bones.htm ‡ Thymic hyperplasia (65%), thymoma (15%) ‡ Clinical: extraocular muscles (ptosis, diplopia) Æ generalized weakness, respiratory paralysis ‡ Rx: anticholinesterase agents, prednisone, plasmapheresis, resection of thymoma